Ask about this productRelated genes to: TLR4 antibody
- Gene:
- TLR4 NIH gene
- Name:
- toll like receptor 4
- Previous symbol:
- -
- Synonyms:
- hToll, CD284, TLR-4, ARMD10
- Chromosome:
- 9q33.1
- Locus Type:
- gene with protein product
- Date approved:
- 1998-06-25
- Date modifiied:
- 2016-01-21
Related products to: TLR4 antibody
Related articles to: TLR4 antibody
- Ulcerative colitis (UC) is a growing global health burden, creating an urgent need for new therapies. While extracellular vesicles (EVs) from probiotic bacteria show therapeutic potential, their molecular mechanisms are largely unknown. This study reveals that Lactobacillus paracasei (LPC) and its EVs (LPC-EVs) alleviate Dextran Sulfate Sodium Salt (DSS)-induced colitis in mice through a multi-faceted mechanism involving partial reshaping of the gut microbiota, suppression of TLR4/NF-κB signaling, and reinforcement of tight junctions. We found that miR-9394b carried by LPC-EVs plays a central role in this effect. In MODE-K cells, miR-9394b directly targets iNOS, shifting arginine metabolism away from nitric oxide (NO) production toward ornithine-associated metabolism. The increased ornithine served as a downstream mediator linking epithelial metabolic remodeling to macrophage polarization. Collectively, these findings support a model in which bacterial EVs mediate the transfer of miR-9394b to coordinate a metabolic-immune response, highlighting a potential avenue for miRNA-guided intervention in experimental colitis. - Source: PubMed
Publication date: 2026/05/25
Ding HonghaoZhang HengLi DiyingHu ZhiqiXiang GuoqiNie QingqingLiu QibingLiang YunxiangWang ShuaiTao ShiyuLi Yingjun - Monocyte-macrophage lineage cells, crucial components of the innate immune system, can uniquely form bone-resorbing osteoclasts upon exposure to the cytokine receptor activator of nuclear factor κB ligand (RANKL) in the bone microenvironment. Recent studies have also begun to uncover extensive extraskeletal roles of RANKL. However, how monocyte-macrophage lineage cells respond to RANKL outside of the bone, and the impact that this signaling pathway exerts on the host immune response, is not fully understood. In this study, we sought to define how RANKL exposure shapes the macrophage inflammatory response to pathogens by using the model intracellular bacterium Salmonella enterica serovar Typhimurium, which coopts macrophages to cause life-threatening infections. We found that exposing both mouse and human macrophages to subosteoclastogenic levels of RANKL increased intracellular Salmonella enterica serovar Typhimurium burdens and decreased proinflammatory cytokine production. RNA sequencing revealed downregulation of pattern recognition receptor signaling pathways in RANKL-treated macrophages during the early stages of infection. Therefore, we hypothesized that RANKL impairs pattern recognition receptor-dependent signaling pathways that are important for proinflammatory cytokine production. We discovered that RANKL-treated macrophages exhibit reduced nuclear factor κB and interferon regulatory factor 3 activation, specifically in response to Toll-like receptor 2 (TLR2) and TLR4 stimulation. We determined that prior RANKL exposure decreases abundance of the TLR2 and TLR4 adaptor proteins TRAM (TRIF-related adaptor molecule) and TIRAP (TIR domain-containing adaptor protein). Together, these data suggest that RANKL exposure negatively impacts the macrophage TLR-mediated inflammatory response to bacteria. - Source: PubMed
Si Clara DPeek Christopher TFatah Sana RBeaudoin Andrew JZhelonkin Anton REichelberger Kara RHahn Stacy LWatson Robert OMogilenko Denis ACassat James E - Mycoplasma pneumoniae (Mp) is a major pathogen of community-acquired pneumonia increasingly resistant to macrolides. Mp infection provokes oxidative stress, disrupts epithelial integrity, and skews T helper (Th) cell balance through CARDS toxin-mediated immune dysregulation. Here, we investigated the protective effects of melatonin, a pleiotropic hormone with antioxidant and immunomodulatory functions, in patients and a murine model of Mp pneumonia. Mp infection perturbed the local Th1/Th2/Th17 balance, accompanied by ROS accumulation, CXCL10-induced TLR4/STAT1 activation, and loss of ZO1-dependent tight junctions. Melatonin administration suppressed ROS production, restored epithelial barrier integrity, and rebalanced Th responses within the airway microenvironment. Mechanistically, melatonin inhibited CXCL10-TLR4/STAT1 signaling, with TLR4 residue A366 identified as a key regulatory site. These findings reveal that melatonin alleviates Mp-induced airway injury by maintaining immune and epithelial homeostasis, highlighting its potential as an adjunctive therapy for macrolide-resistant Mp pneumonia. - Source: PubMed
Publication date: 2026/05/23
Lee Chun-YiWu Tsung-HuaSheu Meei-LingChiang Wen-HsuanPan Hung-ChuanFang Yu-PingTsai Yi-ChingTsai Chia-YunLai De-Wei - Endotoxin tolerance (ET) represents a hyporesponsive state of the innate immune system that develops following prior exposure to endotoxins like lipopolysaccharide (LPS), a potent Toll-like receptor 4 (TLR4) agonist. While ET has been extensively studied in peripheral monocytes and macrophages, its implications within the central nervous system (CNS) remain insufficiently understood. As the resident innate immune cells of the CNS, microglia are central to the regulation of neuroinflammation and can either exacerbate or ameliorate neuronal injury depending on their activation state. Emerging evidence indicates that LPS preconditioning induces microglia-mediated ET, a state that attenuates excessive inflammation and preserves CNS homeostasis. In this review, we synthesize current insights into the concept of ET and elucidate the molecular mechanisms underlying microglial reprogramming, focusing on the coordination of signaling pathways, epigenetic modifications, and metabolic shifts that drive the tolerant phenotype. Within the framework of innate immune memory, we compare ET with trained immunity to highlight their distinct context-dependent effects. Evidence from in vitro co-culture systems and in vivo models of acute CNS injury, neurodegenerative disorders, epilepsy, and psychiatric-like behaviors indicates that LPS preconditioning-induced microglia-mediated ET can confer neuroprotection. We will address the paradox of neuroprotection by LPS preconditioning, underscore the translational potential of LPS-derived TLR4 modulators, and propose future directions for harnessing microglia-mediated ET as a therapeutic strategy for CNS diseases. - Source: PubMed
Publication date: 2026/05/23
Dong LaDoorduin Janinede Vries Erik F J - According to the "Old Friends" hypothesis, the increased prevalence of stress-associated disorders in urban concrete landscapes of high-income countries is at least in part due to a reduced exposure to immunoregulatory microorganisms. The latter is particularly impactful when occurring during early prenatal and postnatal life. Accordingly, our own preclinical studies demonstrate that non-pathogenic rapid-growing mycobacteria, including Mycobacterium (M.) vaccae NCTC 11659 and M. vaccae ATCC 15483, have immunoregulatory and stress-protective effects when administered repeatedly prior to or during stressor exposure. Here, we advance these findings by showing that repeated intragastric (i.g.) administration of a heat-killed preparation of M. vaccae ATCC 15483 to female C57BL/6 N mice provides intergenerational stress protection. Their male offspring, despite never directly receiving administration of rapid-growing mycobacteria, were protected against multiple adverse consequences of chronic stress in adulthood. Moreover, correlational analyses implicate the fecal microbiome as a potential mediator of these effects, with M. vaccae ATCC 15483 intergenerationally facilitating α-diversity and increasing the relative abundance of bacterial taxa known to be potent short-chain fatty acid producers. Repeated intragastric (i.g.) administration of a heat-killed preparation of Mycobacterium (M.) vaccae ATCC 15483 (MvacATCC)vs. its vehicle borate-buffered saline (BBS) to adult nulliparous female C57BL/6N mice was intergenerationally protective against multiple negative physiological and immunological consequences of chronic subordinate colony housing (CSC; compared with respective single-housed control (SHC) mice), including adrenal hypertrophy, splenomegaly, thymus involution, and tibia growth reduction as well as increased splenic toll-like receptor (TLR) 2 and TLR4 protein concentrations and splenocyte ex vivo (re)activity, but also decreased splenic ex vivo glucocorticoid sensitivity, regulatory T cell (Treg) counts and Treg suppression capacity in their male offspring. In contrast, CSC-induced increase in splenic myeloid cell counts as well as of neutrophilic chemotactic activity was not affected intergenerationally by MvacATCC. Moreover, fecal microbiome analyses before and after CSC showed that MvacATCC intergenerationally facilitated α-diversity and relative abundance of bacterial taxa known to be potent short-chain fatty acid (SCFA) producers. Of note, we abstained from showing respective data of female offspring in the graphical abstract (*), as the intergenerational resilience effects of MvacATCC on female offspring were difficult to interpret. The latter was due to the fact that chronic adult stressor exposure (i.e., social instability paradigm, SIP) per se did not affect any of the physiological and immunological readouts reported in females. The graphical abstract was created with Biorender.com. - Source: PubMed
Publication date: 2026/05/22
Schiele JessicaTsai Pei-LingSchimmele TamaraBeck SinaMeyer MarenMannes MarcoDesmond Luke WNoschka ReinerHuber-Lang MarkusHaffner-Luntzer MelanieJarczok Marc NLowry Christopher AReif AndreasLanggartner DominikStenger SteffenSlattery David AReber Stefan O